GOP strategists said lawmakers would use such a nomination as an opening for an extended examination of how the administration handled the Sept. 11 militant attack on the U.S. mission in Benghazi, Libya, that killed four Americans, including the U.S. ambassador. Although the Senate rarely rejects a president’s Cabinet picks, the strategists said, the process could be so painful and lengthy that Obama might come to regret his choice.

A senior Republican aide said he couldn’t predict whether the nomination would be voted down, but “the question is, is this worth spending political capital and taking punches on a subject they’d like to distance themselves from?”

“Whether it’s fair to her or not, she’s become a poster child for perceptions that there’s been a cover-up by the administration,” he said, speaking anonymously because he was not authorized to speak publicly.

Some Senate Republicans have already begun discussing how they would question Rice, he said, and plan to gather information from House Republican colleagues to bore in on questions the administration has not yet satisfactorily answered.

Sen. Jon Kyl, R-Ariz., the No. 2 Senate Republican, told reporters he considered Rice “tainted” by her role in the administration’s handling of Benghazi, and recommended that the White House instead choose Sen. John Kerry, D-Mass., chairman of the Senate Foreign Relations Committee, whom administration officials have also been considering for the diplomatic post.

Administration officials said that Rice, a pillar of Obama’s foreign policy team since the 2008 election campaign, was a leading candidate for the post, and that they would not be deterred by Republican warnings. Officials and some others familiar with the process predicted that the GOP would eventually end their resistance to Rice because it would become clear that her disputed comments after the attack were prepared by other U.S. officials for her appearances on Sunday Sept. 16 talk shows.

Rice said in those TV appearances that the attack was motivated by anger at a U.S.-made film trailer that denounced the prophet Muhammad, and that it was not a planned terrorist assault.

Sen. Bob Corker, R-Tenn., who is expected to become the ranking minority member of the Senate Foreign Relations Committee, found it “beyond belief” that Rice could have described the attack as motivated by anger over the film, when U.S. officials in Benghazi had told officials in Washington during the attack that it was a terrorist assault.

“I still don’t know how anybody of that capacity could have been on television five days later saying the things that were said,” Corker said. “I don’t know how that could happen.”

On Sunday, Sen. Lindsey Graham of South Carolina, an influential Republican on foreign policy issues, predicted that Rice’s nomination would have a difficult time making it through the Senate. He said he would not vote for Rice unless she provided more satisfactory explanations of her actions.

A single senator can hold up a nomination if he or she is determined to do so. But a more likely avenue to blocking confirmation would be with a filibuster, aides said. Sixty votes are required to end a filibuster – fewer than the number of senators in the Democratic caucus.

Senate aides said the Republican caucus, which is regrouping after the election defeat, might decide that shooting down Obama’s choice would be a way of underscoring its unhappiness with the administration’s treatment of the Benghazi issue. But historically, the Senate has deferred to presidents on Cabinet picks, and Republicans would run the risk of looking unreasonable.

Clinton’s intention to leave the post has been public for more than a year, and the candidacies of Rice and Kerry have been discussed for months. Both are known to be interested in the job.

The Washington Post reported Tuesday that Rice was the leading candidate for the diplomatic post and Kerry, a Vietnam veteran, was under consideration as secretary of defense. If Kerry took either post, Republicans would have a chance to win his Senate seat in a special election – winnowing the Democrats’ narrow majority.